Attitudes, Knowledge, and Risk Perceptions of Patients who Received Elective Genomic Testing as a Clinical Service.

BACKGROUND: Elective genomic testing (EGT) is increasingly available clinically. Limited real world evidence exists about attitudes and knowledge of EGT recipients. METHODS: After web-based education, patients who enrolled in an EGT program at a rural nonprofit healthcare system completed a survey that assessed attitudes, knowledge, and risk perceptions. RESULTS: From August 2020 to April 2022, 5,920 patients completed the survey and received testing. Patients most frequently cited interest in learning their personal disease risks as their primary motivation. Patients most often expected results to guide medication management (74.0%), prevent future disease (70.4%), and provide information about risks to offspring (65.4%). Patients were "very concerned" most frequently about the privacy of genetic information (19.8%) and how well testing predicted disease risks (18.0%). On average, patients answered 6.7 of 11 knowledge items correctly (61.3%). They more often rated their risks for colon and breast cancers as lower rather than higher than the average person, but more often rated their risk for a heart attack as higher rather than lower than the average person (all p<0.001). CONCLUSION: Patients pursued EGT because of the utility expectations, but often misunderstood the test's capabilities.

Familial communication and cascade testing following elective genomic testing.

Familial communication of results and cascade genetic testing (CGT) can extend the benefits of genetic screening beyond the patient to their at-risk relatives. While an increasing number of health systems are offering genetic screening as an elective clinical service, data are limited about how often results are shared and how often results lead to CGT. From 2018 to 2022, the Sanford Health system offered the Sanford Chip, an elective genomic test that included screening for medically actionable predispositions for disease recommended by the American College of Medical Genetics and Genomics for secondary findings disclosure, to its adult primary care patients. We analyzed patient-reported data about familial sharing of results and CGT among patients who received Sanford Chip results at least 1 year previously. Among the patients identified with medically actionable predispositions, 94.6% (53/56) reported disclosing their result to at least one family member, compared with 46.7% (423/906) of patients with uninformative findings (p < 0.001). Of the patients with actionable predispositions, 52.2% (12/23) with a monogenic disease risk and 12.1% (4/33) with a carrier status reported that their relatives underwent CGT. Results suggest that while the identification of monogenic risk during elective genomic testing motivates CGT in many at-risk relatives, there remain untested at-risk relatives who may benefit from future CGT. Findings identify an area that may benefit from increased genetic counseling and the development of tools and resources to encourage CGT for family members.

Clinically Indicated Genomic Sequencing of Children in Foster Care: Legal and Ethical Issues.

There are approximately 400 000 children in foster care in the US, approximately one-half of whom have chronic health problems and approximately 10% of whom have complex healthcare needs. Given the increasing relevance of genomic sequencing to guide clinical care for children with rare, chronic, and undiagnosed conditions, it may be an important component of diagnostic evaluation for children in foster care. Clinically indicated genomic sequencing may provide information that has health implications for children in foster care, as well as for their biological parents and other relatives. Whether and how genomic sequencing results impact legal decision making and family court outcomes is not yet well-understood. We describe scenarios that highlight legal, ethical, and policy issues surrounding genomic sequencing for children in foster care using 3 cases adapted from real-world events. Together, these cases highlight important yet underexplored issues that arise when genomic information has legal relevance in family court and ethical implications for child and family well-being. As genomic sequencing becomes more routine for the general pediatric population, additional research is needed to better understand its impacts on children and other stakeholders within the foster care system.

Clinical impact of preemptive pharmacogenomic testing on antiplatelet therapy in a real-world setting.

CYP2C19 genotyping to guide antiplatelet therapy after patients develop acute coronary syndromes (ACS) or require percutaneous coronary interventions (PCIs) reduces the likelihood of major adverse cardiovascular events (MACE). Evidence about the impact of preemptive testing, where genotyping occurs while patients are healthy, is lacking. In patients initiating antiplatelet therapy for ACS or PCI, we compared medical records data from 67 patients who received CYP2C19 genotyping preemptively (results >7 days before need), against medical records data from 67 propensity score-matched patients who received early genotyping (results within 7 days of need). We also examined data from 140 patients who received late genotyping (results >7 days after need). We compared the impact of genotyping approaches on medication selections, specialty visits, MACE and bleeding events over 1 year. Patients with CYP2C19 loss-of-function alleles were less likely to be initiated on clopidogrel if they received preemptive rather than early or late genotyping (18.2%, 66.7%, and 73.2% respectively, p = 0.001). No differences were observed by genotyping approach in the number of specialty visits or likelihood of MACE or bleeding events (all p > 0.21). Preemptive genotyping had a strong impact on initial antiplatelet selection and a comparable impact on patient outcomes and healthcare utilization, compared to genotyping ordered after a need for antiplatelet therapy had been identified.

Framing the Family: A Qualitative Exploration of Factors That Shape Family-Level Experience of Pediatric Genomic Sequencing.

Families of children with rare and undiagnosed conditions face many psychosocial and logistical challenges that may affect their approach to decisions about their child's care and their family's well-being. As genomic sequencing (GS) is increasingly incorporated into pediatric diagnostic workups, assessing the family-level characteristics that shape the experience of pediatric GS is crucial to understanding how families approach decision-making about the test and how they incorporate the results into their family life. We conducted semi-structured interviews with parents and other primary caregivers of pediatric patients who were evaluated for a suspected genetic condition and who were recommended to have GS (n = 20) or who had recently completed GS (n = 21). We analyzed qualitative data using multiple rounds of thematic analysis. We organized our thematic findings into three domains of factors that influence the family-level experience of GS: (1) family structure and dynamics; (2) parental identity, relationships, and philosophies; and (3) social and cultural differences. Participants conceptualized their child's family in various ways, ranging from nuclear biological family to support networks made up of friends and communities. Our findings can inform the design and interpretation of preference research to advance family-level value assessment of GS as well as genetic counseling for families.

Attitudes about pharmacogenomic testing vary by healthcare specialty.

Aim: To understand how attitudes toward pharmacogenomic (PGx) testing among healthcare providers varies by specialty. Methods: Providers reported comfort ordering PGx testing and its perceived utility on web-based surveys before and after genetics education. Primary quantitative analyses compared primary care providers (PCPs) to specialty providers at both timepoints. Results: PCPs were more likely than specialty care providers to rate PGx testing as useful at both timepoints. Education increased comfort ordering PGx tests, with larger improvements among PCPs than specialty providers. Over 90% of cardiology and internal medicine providers rated PGx testing as useful at pre- and post-education. Conclusion: PCPs overwhelmingly perceive PGx to be useful, and provider education is particularly effective for improving PCPs' confidence. Education for all specialties will be essential to ensure appropriate integration into routine practice.

SLCO1B1 gene-based clinical decision support reduces statin-associated muscle symptoms risk with simvastatin.

Background: SLCO1B1 variants are known to be a strong predictor of statin-associated muscle symptoms (SAMS) risk with simvastatin. Methods: The authors conducted a retrospective chart review on 20,341 patients who had SLCO1B1 genotyping to quantify the uptake of clinical decision support (CDS) for genetic variants known to impact SAMS risk. Results: A total of 182 patients had 417 CDS alerts generated, and 150 of these patients (82.4%) received pharmacotherapy that did not increase risks for SAMS. Providers were more likely to cancel simvastatin orders in response to CDS alerts if genotyping had been done prior to the first simvastatin prescription than after (94.1% vs 28.5%, respectively; p < 0.001). Conclusion: CDS significantly reduces simvastatin prescribing at doses associated with SAMS.

Barriers and facilitators to physical education, sport, and physical activity program participation among children and adolescents with psychiatric disorders: a systematic review.

Children and adolescents with heterogeneous psychiatric disorders, of whom over 50% have a second psychiatric comorbidity, have low rates of physical activity and experience unique challenges to engaging in community-based exercise programming, school-based physical education programming, and targeted physical activity interventions. This contributes to elevated rates of gross and fine motor delays, lower mood and self-regulation, and increased risk of chronic diseases such as obesity and type 2 diabetes. Perform a systematic scoping review of the literature to assess known barriers to and facilitators of engaging in physical activity programming among children and adolescents with heterogeneous and/or comorbid psychiatric disorders, in order to improve engagement among this population in real world intervention settings. Systematic Boolean diagnostic and physical activity search terms were entered into PubMed, MEDLINE, PsycINFO and Web of Science for English-language studies published between 2005 and 2020, examining barriers and facilitators for common psychiatric diagnoses and general psychiatric population's engagement in physical activity, physical education, sports, or exercise interventions. Two reviewers independently reviewed titles, abstracts and full articles to determine inclusion. A total of 5,198 articles were returned; 39 relating to children and adolescents were qualified for full-text review. After review, 24 studies were included addressing barriers and facilitators across multiple diagnoses; 7 studies were quantitative, 10 were qualitative, and 7 were mixed methods. Major barriers included low motivation, low self-efficacy, depleted parental reserve capacity, social isolation, lack of staff training, and safety concerns. Major facilitators included peer support/engagement, exergames, supportive parental behaviors, and inclusive/adaptive programming. Numerous barriers and facilitators to physical activity have been identified which should inform community, school, clinical, and research intervention program design. Further research is needed to develop effective strategies that address the challenges to inclusion that children and adolescents with heterogeneous and/or comorbid psychiatric disorders face.